Mao Liang, Fan Teng-Fei, Wu Lei, Yu Guang-Tao, Deng Wei-Wei, Chen Lei, Bu Lin-Lin, Ma Si-Rui, Liu Bing, Bian Yansong, Kulkarni Ashok B, Zhang Wen-Feng, Sun Zhi-Jun
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, China.
Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Cell Mol Med. 2017 Sep;21(9):2199-2210. doi: 10.1111/jcmm.13143. Epub 2017 Apr 11.
Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7-H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7-H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7-H3 blockade as a future therapeutic strategy to treat patients with HNSCC.
包括髓系来源的抑制细胞（MDSCs）和肿瘤相关巨噬细胞（TAMs）在内的未成熟髓样细胞，通过促进肿瘤转化和血管生成以及抑制抗肿瘤效应免疫反应，来促进肿瘤生长和转移。因此，旨在减少MDSCs和TAMs的积累及其活性的策略是潜在有价值的治疗目标。在本研究中，我们发现与正常口腔黏膜相比，负性免疫检查点分子B7-H3在人头颈部鳞状细胞癌（HNSCC）标本中显著过表达。使用具有免疫活性的转基因HNSCC模型，我们观察到靶向抑制B7-H3可减小肿瘤大小。流式细胞术分析表明，靶向抑制B7-H3可通过减少免疫抑制细胞并促进肿瘤微环境和宏观环境中的细胞毒性T细胞活化来增强抗肿瘤免疫反应。我们的研究为B7-H3阻断作为治疗HNSCC患者的未来治疗策略提供了直接的体内证据。
